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Ann Thorac Surg 2001;71:769-776
© 2001 The Society of Thoracic Surgeons
a Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
b Center for the Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, New Hampshire, USA
c Maine Medical Center, Portland, Maine, USA
d Catholic Medical Center, Manchester, New Hampshire, USA
e Eastern Maine Medical Center, Bangor, Maine, USA
f Fletcher Allen Health Care, Burlington, Vermont, USA
g Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Accepted for publication June 14, 2000.
Address reprint requests to Mr DeFoe, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03756
e-mail: gordon.defoe{at}hitchcock.org
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Abstract |
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 Top Abstract IntroductionMaterial and methodsResultsCommentAcknowledgmentsAppendix. Northern New England...References |
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Methods. We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category.
Results. After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass.
Conclusions. Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsAppendix. Northern New England...References |
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Material and methods |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsAppendix. Northern New England...References |
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Data used in these analyses included: patient age, gender, and body surface area (BSA); comorbid conditions other than heart disease (chronic obstructive pulmonary disease, diabetes, peripheral vascular disease, preexisting renal failure, preexisting peptic ulcer disease, liver disease, cancer); prior CABG (yes or no); cardiac catheterization results (degree of left main coronary artery stenosis, total number of significantly diseased vessels, left ventricular end-diastolic pressure, ejection fraction); priority of surgery (emergency, urgent, or elective); preoperative hematocrit; lowest hematocrit during bypass. The dependent variables include: intra- or postoperative use of an intraaortic balloon pump (IABP); intra- or postop stroke; return to bypass after initial separation; return to the operating room for the treatment of postop thoracic bleeding (or postoperative hemorrhage); and vital status at hospital discharge.
Cardiac catheterizations were performed at the participating or referring institutions using their own standard methods during the course of regular clinical care. Ejection fractions were scored using the method described by Pierpont and colleagues [8]. The number of diseased coronary vessels was scored using methods adapted from the National Heart, Lung, and Blood Institute Coronary Artery Surgery Study [9].
The comorbidity score used in this study is based on the work by Charlson and coworkers [10]. The cardiothoracic surgeons, using definitions previously described, assessed priority of surgery [11]. Briefly, they are defined as follows: emergency (medical factors relating to the patient’s cardiac disease dictate that surgery should be performed within hours to prevent morbidity or death); urgent (medical factors require the patient stay in-hospital to have an operation before discharge); and elective (medical factors indicate the need for operation, but the clinical situation allows discharge from the hospital for readmission at a later date).
The lowest hematocrit on bypass was defined as the lowest recorded hematocrit prior to weaning from the initial pump run. A category variable was created for hematocrit based on the distribution of values. The category variable had the following cut points: less than 19%, 19% to 20%, 21% to 22%, 23% to 24%, greater than or equal to 25 (Fig 1).
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Statistical methods
Standard statistical methods were used to calculate the crude event rates and mean lowest hematocrit values by subgroup. Risk-adjusted rates and tests of trend across the five categories of hematocrit were calculated using logistic regression [12]. Patient and disease variables used to adjust the event rates come from previous work in modeling risk for each individual outcome.
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Results |
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Table 1 summarizes the patient and disease characteristics by categories of nadir hematocrit during CPB. The data are stratified by the patient’s gender. These data show that women are more likely to be in the lower hematocrit groups. Among both men and women, older patients and patients with a lower BSA are more prevalent in the lower hematocrit levels. Comorbid conditions [diabetes, peripheral vascular disease (PVD), and preoperative congestive heart failure (CHF)] are more prevalent in the lower hematocrit levels. Chronic obstructive pulmonary disease (COPD) and preoperative renal failure show somewhat different results for men and women. There is a significant trend toward higher prevalence of these comorbid conditions among men but not women. This is somewhat difficult to evaluate because of the substantially smaller number of women in these data. Not surprisingly patients with higher preoperative hematocrit values were more likely in the higher levels of nadir hematocrit. Prior CABG surgery was more common in the lower hematocrit levels among men but not among women. Left ventricular end-diastolic pressure (LVEDP) was not significantly associated with nadir hematocrit levels and left ventricular ejection fraction was only weakly associated with nadir hematocrit levels among men. Left main stenosis was associated with nadir hematocrit levels among men as was priority at surgery. Only emergency surgery was associated with nadir hematocrit among women.
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25%). The association between lowest hematocrit during CPB and increased risk of in-hospital mortality was observed at all medical centers. The rate of intraoperative or postoperative IABP use was associated (p[trend] < 0.001) with lowest hematocrit measured during cardiopulmonary bypass. Intra- or postoperative IABP use was 6.1% among those in the lowest category and 3.6% among those in the highest category. Return to CPB was also associated (p[trend] < 0.001) with the lowest hematocrit measured during the initial bypass run. Those in the lowest category of hematocrit had substantially higher rates of return to bypass (7.5% versus 3.8%) than did those in the highest category. Neither postoperative stroke (p[trend] = 0.736) nor return to the operating room for the treatment of bleeding (p[trend] = 0.310) was associated with lowest hematocrit during cardiopulmonary bypass. In each case, the same effect was seen in the adjusted and the crude results. However, the risk-adjusted rates show a smaller magnitude of effect than do the crude rates.
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Comment |
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We conducted a regional observational study and this design is vulnerable to a number of possible threats to validity. In our view, these results are unlikely to be a consequence of chance, bias, or confounding. The data set is large, the observed results are highly statistically significant, and data were obtained from multiple medical centers employing identical data definitions. These results persisted after multivariate adjustment for a variety of patient and disease characteristics, and were consistent across medical centers. This was not a treatment study. Therefore, it does not provide any direct proof that avoidance of hemodilutional anemia would yield better clinical outcomes.
Only a few other large studies have examined the association between lowest hematocrit during CPB, and risk of death and adverse outcomes among CABG patients. Fang and colleagues reported on the association between the lowest hematocrit during CPB and mortality among 2,738 CABG surgery patients [7]. They conducted multivariate statistical analyses using a number of hematocrit categories and concluded that a lowest hematocrit of less than or equal to 14% for low-risk patients and less than or equal to 17% for high-risk patients were associated with more than a doubling of risk of death. The current study is in agreement with their findings, and extends these findings by describing the association between lowest hematocrit during CPB and death, as well as other adverse outcomes. Like Fang and associates, we showed a doubling of risk when comparing those with lower to those with higher minimum hematocrit [7]. However, in our regional data, only 0.8% of patients had a lowest hematocrit less than or equal to 14%, and only 7% had a lowest hematocrit less than or equal to 17%. Further, our data showed a trend toward increasing risk of death at all hematocrits below 23%. This includes a much larger group of patients at risk than did the results reported by Fang and colleagues [7]. In a published abstract, Stafford Smith and coworkers reported a study of the association between the lowest hematocrit during CPB and postoperative renal failure [13]. They studied 1,404 first-time CABG patients and found a modest association. Data on mortality were not reported.
Several other studies have examined pre- or postoperative anemia. Hardy and colleagues studied the association between the nadir hemoglobin in the 24 hours after surgery and major morbidity among 2,664 cardiac surgery patients [14]. They found that the minimum hemoglobin concentration was associated with major morbidity (eg, hemodynamic instability, renal failure). Intraoperative deaths were excluded from this study since their nadir 24-hour hematocrit could not be assessed. Carson and colleagues studied the risk of death and morbidity among 1,958 noncardiac surgical patients [15]. All had declined blood transfusion for religious reasons. They found that a low preoperative hemoglobin or substantial operative blood loss increased the risk of serious morbidity or death. This effect was significantly more pronounced among patients with cardiovascular disease. They concluded that even mild anemia is associated with some increased risk of perioperative death, and that patients with cardiovascular disease have a substantially greater risk.
In the current study, we have found a significant association between low hematocrit and return to bypass after attempted separation, need for an intra- or postoperative IABP and mortality. We found no significant association between lowest hematocrit during CPB and either postoperative bleeding or stroke. These findings suggest low cardiac output as a common mechanism. Is it plausible that a low hematocrit during CPB could cause these effects? In previously published studies, we have shown that approximately two-thirds of deaths following CABG surgery are a consequence of low cardiac output syndrome, and that the majority of patients developing low output had preserved left ventricular function before surgery [16]. These studies have also shown that much of the excess mortality among women is a consequence of low cardiac output syndrome and that small BSA was associated with perioperative mortality [17, 18]. These previous findings are consistent with the findings of the current study.
The association of low hematocrit to failed separation, the need for balloon support, and death suggests the possibility that a biologic mechanism in the myocardium may be at work. The relationship of low hematocrit to perioperative myocardial ischemia is uncertain, since the balance of oxygen supply and demand during CPB is complex and dynamic. Oxygen delivery is impacted by low hematocrit, but dropping blood viscosity and vascular resistance improve flow of anemic blood in partial compensation [19]. Second, the period of exposure of the myocardium to the diluted blood of the CPB circuit is limited by the aortic cross-clamp, but residual myocardial blood flow via bronchial vasculature and noncoronary collaterals is not uncommon [20]. Many cardioplegia regimens are based upon CPB circuit blood, usually after further hemodilution with a potassium-rich solution, exposing the myocardium to a low hematocrit. On the other hand, based on the 1997 Society of Thoracic Surgeons data, 19.7% of CABG surgery is performed using clear crystalloid cardioplegia for primary myocardial protection and there was no significant association of this technique with death [21]. We conclude that the hypothesis that a low hematocrit is a specific cause of intraoperative myocardial damage is plausible but not proven. Studies of markers of myocardial damage such as troponin or creatine kinase may be useful in further studies.
In the current study, small patients and those with lower preoperative hematocrit were much more likely to have a low hematocrit during bypass. This is not a surprising finding, since the use of standard size CPB circuits would cause more hemodilution among smaller patients and those with a lower preoperative hematocrit. A number of studies have found small BSA to be associated with risk of death [17]. The current study suggests a possible mechanism for the prior findings. We found no substantial difference in the risk-adjusted rate of death between men and women with a similar intraoperative hematocrit (Fig 2). This suggests that some of the increased risk observed among women undergoing CABG surgery may be a consequence of a greater incidence of hemodilutional anemia during cardiopulmonary bypass.
If this association between lowest hematocrit during CPB and risk of return to bypass, the need for left ventricular assist, and in-hospital death is causal, it is a modifiable risk factor. Several changes in the process of care for CABG patients may decrease the likelihood of hemodilutional anemia. These include: an increased attention to blood loss in the preoperative period as a consequence of phlebotomy and cardiac catheterization; preoperative estimation of the risk of hemodilutional anemia based on the patient’s hematocrit, sex, and BSA; the redesign of CPB circuits to better match the size of the patients; the reconsideration of the methods of managing perioperative blood loss, especially the timing of return of collected blood; the perioperative management of colloids and crystalloids to avoid excessive hemodilution; and the reconsideration of autologous and homologous transfusion practices [1, 18, 22–24].
This regional observational study found a strong association between the lowest hematocrit during CPB and risk of return to bypass, need for intraaortic balloon support, and in-hospital death. These data showed a trend toward increasing risk of death for patients with a hematocrit below 23%, while those with hematocrit less than 19% had mortality rates approximately twice as high as those greater than or equal to 25%. These effects persisted after multivariate adjustment for preoperative differences in patient and disease characteristics. These effects were seen among both women and men, but women and small men were much more likely to be in the low hematocrit group. This finding suggests that the anemia is largely a consequence of hemodilution. It is plausible that this association between lowest hematocrit during CPB is causal, but it is not proven. Subsequent studies using biological markers of myocardial damage may be useful to further understand this association. (Appendix)
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Acknowledgments |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsAppendix. Northern New England...References |
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Stephen J. Lahey, MD, and Mary E. Bogosian, RN, are now with the Worcester Medical Center, Worcester, Massachusetts. Peter Marshall, MD, is now with the Central Maine Medical Center, Lewiston, Maine.
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Appendix. Northern New England Cardiovascular Disease Study Group |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsAppendix. Northern New England...References |
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Catholic Medical Center, Manchester, NH
Stephanie Bagg, MS, Yvon Baribeau, MD, Ann Becker, RN, Donna Bennett, RN, Craig C. Berry, MD, Stephen Bogursky, MD, William A. Bradley, MD, Lois Brown, RN, Steven Buergin, PA, David C. Charlesworth, MD, Diane Cherwin, RN, Arlone Cofield, RN, Susan Cuddy, BSN, CCRN, Helen Desaulniers, RN, Robert C. Dewey, MD, Louis I. Fink, MD, Alan E. Garstka, MD, Karen Grafton, RN, Kathy Gronowski, MS, Deborah Haines, RN, Dan Halstead, CCP, Michael J. Hearne, MD, J. Beatty Hunter, MD, Dennis Kelly, MD, Peggy Lambert, RN, Patrick J. Lawrence, MD, Elaine Lernard, MS, Christopher T. Maloney, MD, Ann Matheson, RN, Mary McGowan, MD, Katherine McNeil, RN, Karen Mooers, RN, Edward Palank, MD, Carmen Petrin, RN, John Pieroni, MS, Alyson Pitman-Giles, MS, Kevin Potter, MD, Diane Rogier, Mary Sanford, RN, NP, Kenneth Shann, MS, Judy Tsiorbas, ARNP, MSN, Benjamin M. Westbrook, MD, Diane White, RN, Joyce Worrey, RN
Dartmouth Hitchcock Medical Center, Lebanon, NH
John Butterly, MD, Cynthia Hart Bolduc, RN, Gregg S. Hartman, MD, Mary Catherine Hoh, RN, Joy M. Steinkraus, PA, John C. Baldwin, MD, Paul B. Batalden, MD, Virginia Beggs, MS, ARNP, John D. Birkmeyer, MD, Nancy O’Connor Birkmeyer, PhD, MS, George Blike, MD, Judy Boehm, RN, Marlene Bristol, RN, William C. Burke, RCVT, Cheryl Carlson, RN, Edward Catherwood, MD, Karen Chandler, RN, Gene Corliss, RN, Susan D’Anna, ARNP, Lindsay D’Anna, PA, Lawrence J. Dacey, MD, Norman Dame, CCP, Carrie Davis, RN, Gordon DeFoe, CCP, David Dewey, RN, Ken Dixon-Vestal, RN, Thomas Dodds, MD, Mark Farrell, CCP, Mary P. Fillinger, MD, Bruce Friedman, MD, Paul B. Gardent, MBA, Barbara Gerling, MD, D. David Glass, MD, Mark Greenberg, MD, Christine Heins, RN, Bruce D. Hettleman, MD, Peter Holzberger, MD, Douglas James, MD, John Jayne, MD, Karen Jean, RN, Pamela Jenkins, MD, PhD, MS, Lisa C. Johnson, MBA, Joseph F. Kasper, ScD, Lori Key, RN, Terry Kneeland, MPH, Judy Kobe, RN, Samuel Lau, MD, Donny Likosky, MS, Marianne Lillard, BSN, Mike Losos, RN, Betsy Maislen, ARNP, David Malenka, MD, Jimmy R. Maneksha, MB, BS, Mike Maroni, RN, Charles A.S. Marrin, MB, BS, Pam McLaren, RN, Mary Beth Menduni, RN, Patricia Mock, RN, John Munoz, MD, Nathaniel Niles, MD, William C. Nugent, MD, Gerald T. O’Connor, PhD, Daniel J. O’Rourke, MD, Elaine Olmstead, BSN, Robert Palac, MD, Melanie Parla, RN, Winthrop D. Piper, MS, Jonathan Plehn, MD, Stephen K. Plume, MD, Lynn Purvines, BSN, Karen Pushee, RN, Hebe Quinton, MS, Athos J. Rassias, MD, John F. Robb, MD, Cathy Ross, MS, John H. Sanders, MD, William C. Schults, MS, Stephen D. Surgenor, MD, MS, Geoff Tarbox, RN, Andrew T. Torkelson, MD, Sandy Williamson, RN, Beth Wolf, MBA, Norman N. Yanofsky, MD
Eastern Maine Medical Center, Bangor, ME
Mae Barker, RN, Susan Borregard, PA, Donna Brobst, RN, Tina Closson, RN, Robert Clough, MD, Dev Culver, Cynthia Downs, RN, MSN, Donna Dunton, RN, BSN, CIC, Melinda Durrange, RN, Carol Gallupe, Rebecca Henry, RN, Felix Hernandez, Jr, MD, Patricia Ann Hofmaster, PhD, Debbie Johnson, MS, John Klemperer, MD, Rolanda Le Crone, Norman Ledwin, Joel Linn, PA, Peter Marshall, MD, Helen McKinnon, RN, Cathy Mingo, RN, MS, Wendy Perkins, RN, Matthew L. Rowe, MD, Dennis Shubert, MD, Sherry Sprague, Erik Steele, MD, Kitty Tambling, Kristine Thomas, PA, Richard Tierney, MD, Laurie True, RN, Peter N. Ver Lee, MD, Tim Ward, RN, Craig Warren, CCP, Cindy Whited, RNC, Robert M. Hoffman, MD, Craig Pedersen, PA, Ted Silver, MD, Eric Steele, DO, Paul vom Eigen, MD
Fletcher Allen Health Care, Burlington, VT
Richard G. Brandenburgh, PhD, Karen Broderick, RN, Pamela Brown, Christina Brownell, RN, John Brumsted, MD, Kevin Carey, MD, Elissa Close, RN, Steve Colmenero, PAC, Stephen R. Crumb, RN, CS, Karen Farrell, ANP, Karen Fragnoli-Munn, RN, MSA, John Frymoyer, MD, Sally Gagnon, RN, Linda Gruppi, RN, Walter D. Gundel, MD, Frank Harris, Peter Higgins, MD, Frank P. Ittleman, MD, David Johnson, MD, Charles Krumholz, CCP, Ann Laramee, RN, Bruce Leavitt, MD, Martin M. LeWinter, MD, Barry Manley, RN, Steve Marcus, PAC, Tommie Murray, RN, Anna Noonan, RN, Mitchell Norotsky, MD, Kim Norton, RN, William Paganelli, MD, Daniel S. Raabe, Jr, MD, Melinda Rabideau, RN, Kathleen Scacciaferro, RN, Joseph D. Schmoker, MD, Janice Smith, RN, Karen Staerkel, RN, Susan Stoner, RN, Christopher Terrien, MD, Edward Terrien, MD, Suzanne Vilord, RN, Matthew W. Watkins, MD
Maine Medical Assessment Foundation, Augusta, ME
Robert B. Keller, MD, David Wennberg, MD, MPH
Maine Medical Center, Portland, ME
Laurence Adrian, PA, Warren D. Alpern, MD, Eric Anderson, Linda Banister, RN, Claire Berg, RN, Seth Blank, MD, John Braxton, MD, Carl E. Bredenberg, MD, David Burkey, MD, Cantwell Clark, MD, Jane Cleaves, RN, Vincent Conti, Paul M. Cox, MD, Deborah Courtney, RN, MSN, Joshua D. Cutler, MD, Desmond Donegan, MD, Richard Forest, CCP, Jim Gillen, PA, Robert Groom, CCP, Wade Hamilton, MD, Tim Hayes, MD, John Heye, Mary Beth Hourihan, MD, Jane Kane, RN, Saul Katz, MD, Mirle A. Kellett, Jr, MD, Robert Kramer, MD, Costas T. Lambrew, MD, F. Stephen Larned, MD, Jan Littlefield, RN, F.L. Lucas, PhD, Richard McFaul, MD, Paul D. McGrath, MD, Jeremy R. Morton, MD, Denise Mucci, RN, Olivier Muff, Edward R. Nowicki, MD, John R. O’Meara, MD, Sheila Parker, RN, Cathy Prouty, RN, Reed D. Quinn, MD, Louis Russo, MD, Thomas J. Ryan, Jr, MD, Susan Seekins, RN, Andrea Scottie Siewers, Kristen Sullivan, Kim Tierney, Karen Tolan, RN, Joan F. Tryzelaar, MD, Kathy Viger, RN, Paul Weldner, MD, Cynthia Westlund, RN, Wanda Whittet, RN
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